Cannabinoid WIN55212-2 impairs peanut-allergic sensitization and promotes the generation of allergen-specific regulatory T cells.

Autor: Angelina A; Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain., Jiménez-Saiz R; Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain., Pérez-Diego M; Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain., Maldonado A; Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain., Rückert B; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland., Akdis M; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland., Martín-Fontecha M; Department of Organic Chemistry, School of Optics and Optometry, Complutense University of Madrid, Madrid, Spain., Akdis CA; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland., Palomares O; Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain.
Jazyk: angličtina
Zdroj: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2022 Apr; Vol. 52 (4), pp. 540-549. Date of Electronic Publication: 2022 Jan 23.
DOI: 10.1111/cea.14092
Abstrakt: Background: Cannabinoids are lipid-derived mediators with anti-inflammatory properties in different diseases. WIN55212-2, a non-selective synthetic cannabinoid, reduces immediate anaphylactic reactions in a mouse model of peanut allergy, but its capacity to prevent peanut-allergic sensitization and the underlying mechanisms remains largely unknown.
Objective: To investigate the capacity of WIN55212-2 to immunomodulate peanut-stimulated human dendritic cells (DCs) and peanut-allergic sensitization in mice.
Methods: Surface markers and cytokines were quantified by flow cytometry, ELISA and qPCR in human monocyte-derived DCs (hmoDCs) and T-cell cocultures after stimulation with peanut alone or in the presence of WIN55212-2. Mice were epicutaneously sensitized with peanut alone or peanut/WIN55212-2. After peanut challenge, drop in body temperature, haematocrit, clinical symptoms, peanut-specific antibodies in serum and FOXP3 + regulatory (Treg) cells in spleen and lymph nodes were quantified. Splenocytes were stimulated in vitro with peanut to analyse allergen-specific T-cell responses.
Results: WIN55212-2 reduced peanut-induced hmoDC activation and promoted the generation of CD4 + CD127 - CD25 + FOXP3 + Treg cells, while reducing the induction of IL-5-producing T cells. In vivo, WIN55212-2 impaired the peanut-induced migration of DCs to lymph nodes and their maturation. WIN55212-2 significantly reduced the induction of peanut-specific IgE and IgG 1 antibodies in serum during epicutaneous peanut sensitization, reduced the clinical symptoms score upon peanut challenge and promoted the generation of allergen-specific FOXP3 + Treg cells.
Conclusions: The synthetic cannabinoid WIN55212-2 interferes with peanut sensitization and promotes tolerogenic responses, which might well pave the way for the development of novel prophylactic and therapeutic strategies for peanut allergy.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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